Human chorionic gonadotropin (hCG) is a member of the glycoprotein hormone family which includes follicle stimulating hormone (FSH), luteinizing hormone (LH) and thyroid stimulating hormone (TSH). These hormones are each composed of two subunits, .alpha. and .beta., which are noncovalently associated, forming a heterodimer. Within a given species the .alpha. subunit is identical whilst the .beta. subunits are different (but homologous) for the different hormones. While the heterodimer is required for receptor binding, it is the .beta.-subunit that confers the specific biological activity to each hormone. The glycoprotein hormones are all heavily glycosylated with N-linked complex carbohydrates, which are a source of natural heterogeneity within a given hormone. hCG is the most heavily glycosylated as it contains an additional four O-linked carbohydrates on the serine rich C-terminal extension of the .beta.-subunit. In human glycoprotein hormones, the common .alpha.-subunit contains 92 amino acids with 10 half-cysteine residues, which form five intramolecular disulphide linkages. The .beta.-subunit polypeptide varies in size from 114 residues in LH, to 145 in CG. The .beta.-subunits contain 12 half cysteines which form six conserved disulphide bridges. Within the first 114 amino acids there is a high degree of sequence homology between hCG and the other hormones (LH 85%; FSH 36%; TSH 46%). The high sequence homology between hCG and LH reflects their common biological function in that both proteins elicit their biological action via the same receptor, whilst FSH and TSH bind to structurally similar, but distinct receptors.
Three-dimensional structure information is useful in being able to display in visual form on a computer screen, the shape of a molecule. The shape may be inspected from different angles by rotation thereof. It may also form the basis for methods of rational drug design. U.S. Pat. No. 5,331,573 discloses a method of rational drug design involving computer simulation of a polypeptide leading to prediction of three-dimensional structure changes which may result from postulated operator-selected changes in peptide chemical structure. U.S. Pat. Nos. 4,704,692 and 4,881,175 disclose computer based systems and methods for converting two naturally aggregated but chemically separate polypeptide chains into a single chain having a similar three-dimensional structure by selecting suitable linker sequences which maintain the original three-dimensional structura.